Problem Session(5) Please provide each reaction mechanisms and explain the stereoselectivities.

Transcription

1 Problem ession(5) Please provide each reaction mechanisms and explain the stereoselectivities iroaki Matoba Boc 1.BF 3 Et 2,C 2 Cl 2,-78 C; allyltm,-78to-20 C 2.MsCl,Et 3,C 2 Cl 2,0 Ctort 81%(2 steps) BDB, 2,-25 Ctort,72% 4.DIBAL,toluene,-78 Ctort,46% Bn 1.a(TM) 2,TF,-80 C; A,-80to-15 C; B,a(TM) 2,18-crown-6-80to-70 C,64% 2.Pb(Ac) 4,,benzene 0 C,95% 2 i C TB 2 C 2-2 Bn C,BF 3 Et 2,C 2 Cl 2,-78 C quant.,dr=15:1 2. Cl, i-prmgcl, TF,-20 C 3.Ac 2,DMAP,C 2 Cl 2,67%(2steps) 4.DIBAL,TF,-78 C,92% 5.D,DBU(cat.),IBX,DM,73% 6.Cu(hfacac) 2 (10mol%),C 2 Cl 2 reflux, 60% Ac 3-2 C 2 Et TBDP Et Et bcl 5 2 i i 2 t-bu 2 BDB A B TBDP C 2 Et D F 3 C Cu II CF 3 F 3 C CF 3 Cu(hfacac) 2

2 Problem ession(5) Topics: ynthetic studies of Lauroxocanes Introduction Laurencia C15 acetogenins Isolated from Laurencia sp.(red algae) cyclic bromoether core(4-12 membered ring) Laroxocanes 8-membered ring ether the largest subset of the Laurencia C15 acetogenins family iroaki Matoba Laurencin Isolation Laurencia glandulifera(irie et al. TL, 1965, 16, 1091.) etc... Total syntheses(method for constructionof oxecene core) Masamune et al. TL, 1977, 18, 2507.(ring expansion: from bicyclo[3.3.1] nonane) Murai and Tsushima TL, 1992, 33, 4345.(ring expansion: from bicyclo[4.2.0] octane) verman et al. JAC, 1995, 117, 5958.(acetal-vinylsulfide cyclizayion) olmes et al. JAC, 1997, 119, 7483.(Baeyer-Villiger oxidation: from cycloheptenone) Crimmins and Emmitte L, 1999, 1, 2029.(RCM) Fujiwaraetal.TL,2005,46,6819.(RCM) Kim et al. L, 2005, 7, 75.(intramolecular amide enolate alkylation) Formal syntheses Palenzuela et al. ynlett, 1996, 983.(2 reaction of -sulfonyl anion to epoxide) ofmann and Krüger JAC, 1997, 119, 7499.(intramolecular allylboration) Crimmins and Choy JAC, 1999, 121, 5653.(RCM) Pansare and Adsool BC, 2008, 6, 2011.(RCM) Martinetal.JC,2010,75,6660.(RCM) West et al. L, 2017, 19, 552.(tevens rearrangement: from bicyclo[4.3.0] nonane) Laurefucin Isolation Laurencia subopposita(wratten and Faulkner JC, 1977, 42, 3343.) etc... Total synthesis Kim et al. JAC, 2008, 130, (intramolecular amide enolate alkylation) Formal synthesis nyder et al. JAC, 2012, 134, (ring expansion: from bicyclo[3.3.0] octane) Laurallene Isolation Laurencia nipponica(fukuzawa and Kurosawa TL, 1979, 20, 2797.) etc... Total syntheses Crimmins and Tabet JAC, 2000, 122, 5473.(RCM) uzuki et al. TL, 2003, 44, 3175.(cyclization of hydroxy epoxide) Kimetal.JAC,2012,134,20178.(RCM) Formal syntheses Takeda et al. L, 2008, 10, 1803.([3+4] annulation) Takeda et al. JC, 2010, 75, 3941.([3+4] annulation) laurencin Ac laurefucin laurallene 1

3 Answer 1. Formal synthesis of(±)-laurefucin nyder et al. JAC, 2012, 134, key: Ring-expanding bromoetherification Boc 1.BF 3 Et 2,C 2 Cl 2,-78 C; allyltm,-78to-20 C 2.MsCl,Et 3,C 2 Cl 2,0 Ctort 81%(2 steps) 3.BDB, 2,-25 Ctort,72% 4.DIBAL,toluene,-78 Ctort,46% Boc Boc BF 3 Et 2 F 3 B i 3 F 3 B i 3 Felkin-Anh model Boc 2 i 3 F 3 B 1-4 Cl Et 3 Boc Boc 1-5 step1 Boc ± + BDB 1-6 Et Et Ms Ms Ms bcl 5 t-bu step2 BDB discussion t-bu 2 Ms Ms step3 2

4 Al i-bu i-bu Al Ms 1-10 Ms 1-11 i-bu i-bu Al Ali-Bu2 DIBAL Ms Ms i-bu 2 Al Ali-Bu 2 i-bu 2 Al 2 Ms steps 1-2 Kimetal JAC, 2008, 130, laurefucin 3

5 Discussion: BDB mediated cyclization 1. Properties and reactivity of BDB(nyder et al. ACIE, 2009, 48, JAC, 2010, 132, ) very effective reagent for cation- cyclization 2. Regio and stereoselectivity ineffective reagent for cation- cyclization Ms di-epi-1-7 Boc Boc Ms disubstituted more electron rich olefin Ms Boc t-bu t-bu Ms di-epi-1-8 Ms di-epi Ms 1-8 Ms R t-bu t-bu too far R 5-exo 6-exo Ms di-epi Ms

6 2. Formal synthesis of(+)-laurallene Takeda et al. L, 2008, 10, key: ook rearrangement mediated[3+4] annulation 1.a(TM) 2,TF,-80 C; A,-80to-15 C; B,a(TM) 2,18-crown-6-80to-70 C,64% 2 i C Bn 2.Pb(Ac) 4,,benzene TB 0 C,95% C 2-2 Bn a 2-1 Bn 2-3 i 2 t-bu Bn discussion TM TM 2 i A t-bu 2 i Bn ook rearr./ cyclopropanation t-bu 2 i 2 i 2-4 i Bn TB i 2 too far TB Bn 2-5a 2-5b i 2 Bn Cope rearr. 2 TB i 2 Bn i TB Bn i 2 Bn TB i TB Bn Ac Ac Pb IV Ac Ac step1 5

7 i Ac Pb(Ac) IV 2 Bn TB i Pb(Ac) IV 2 TB Bn Pb Iv (Ac) 2 2 i Bn TB Pb(Ac) 2 C 2 i C2 TB 2-2 Bn 2 i C TB 2 C 2-2 Bn 10 steps 11 steps TB TB 2-12 Bn Crimmins and Tabet JAC, 2000, 122, laurallene Discussion:[3+4] annulation 1. 1,2-addition a 2 i A 2-3 i 2 t-bu Bn t-bu 2 i Bn i 2 2-4and2-4a TB Bn i 2 2-4' and 2-4a' TB trans Bn i 2 2-4a' favoured 1,2-adduct TB i 2 2-5a-T Bn TB cis Bn TB Bn i 2 2-4' disfavoured 1,2-adduct i T 6

8 2. ook rearrangement-> 1,2-addition t-bu 2 i i Bn t-bu 2 i 2 i 2-5 Bn Internal -i coordinated structure invokes the stereoselectivity. Experiments to trap the intermediate(takeda et al. JAC, 1995, 117, JAC, 1998, 120, 4947.) Attempt to isolate divinylcyclopropane for vinyl silane Li i 2 t-bu 2-14 t-bu 2 i TB 3 i -80 C,30min 3 i TB % i % i % Isolation of related cyclopropane intermediate Li LDA,-80 C,5min 2-17: 25% 2-16: 0% 2-15: 67% i 2 t-bu 2-18 TB 3 i to-30 C 40% i Isolation of divinylcyclopropane for vinyl stannane TB Li TB Bu 3 n i 2 t-bu to-45 C nbu % TB % +2-20(32%) 2-20 Bu 3 n % 7

9 3. Formal synthesis of(+)-laurencin West et al. L, 2017, 19, 552. key: tevenes rearrangement of sulfonium ylide 1.C,BF 3 Et 2,C 2 Cl 2,-78 C,quant. 2. Cl, i-prmgcl, TF,-20 C 3.Ac 2,DMAP,C 2 Cl 2,67%(2steps) 4.DIBAL,TF,-78 C,92% Ac 5.D,DBU(cat.),IBX,DM,73% 6.Cu(hfacac) 2 (10mol%),C 2 Cl reflux, 60% C 2 Et TBDP F 3 B BF 3 Et 2 TBDP TBDP C TBDP 3-4 TBDP 3-5 BF 3 Et 2 TBDP BF TBDP 3-7 TBDP step1 TBDP 3-7 TBDP TBDP 3-8 favoured TBDP 3-9 disfavoured 8

10 ClMg TBDP 3-8 TBDP 3-9 step2 Ac Al Ac TBDP 3-10 step 3 TBDP 3-11 Al i-bu i-bu Et 2 D DBU TBDP Ac Al i-bu i-bu TBDP Ac step4 2 Et Ac TBDP 2 C 2 Et Ac DBU TBDP C 2 Et I Ac TBDP C 2 Et I Ac TBDP C 2 Et step5 9

11 F 3 C F 3 C Cu II CF 3 CF ET F 3 C F 3 C Cu I R C 2 Et F 3 C CF 3 Cu(hfacac) Ac C 2 Et Cu I 3-18 Ac C 2 Et Cu I TBDP 3-17 TBDP 3-21 Ac TBDP Cu I Ac C 2 Et TBDP Cu I C 2 Et Cu I 3-18 Ac Ac C 2 Et tevens rearr. C 2 Et TBDP TBDP solvent cage Ac Ac C 2 Et TBDP C 2 Et TBDP 6steps 3-26 TBDP 8steps olmes et al. JAC, 1997, 119, laurencin Ac 10

12 Discussion: 1. Cu(I) mediated decomposition of diazo compound 1-1. Cu(II) catalyzed cyclopropanation(kochi et al. JAC, 1973, 95, 3300) 2 Et Cu(Tf) 2 (0.68mmol) 1-octene/Ac(5/1) C 2 Et D (mmol) 2 Cu(Tf) 2 wasadded Figure4indicated Afteradditionof1eq.ofDtoCu(II),theyieldof3-27was lessthan20%.(1) AstheadditionofDwascontinued,theyieldof3-27 eventually approached quantitative(based on the incremental ammount of D added.)(2) TheadditionofmoreCu(II)causedasharpdropinthe relative yield of 3-27 (3) Cu(II) reacts with diazo compound firstly and generate Cu(I), which is true active spiecies in this reaction. D(mmol) 1-2. Reaction of Cu(II) salt and diazo compound(ozaki et al. Tetrahedron, 1971, 27, 5353.) Cu(Ac) 2 Ac 2 DMF/ 2,25 C Ac 70% UV-VIspectroscopyofCu(acac) 2 catalyzedcyclopropanation (afiullin et al. Kinetics and Ctalysis, 2008, 49, 43.) 2 Cu(acac) 2 C 2 Cl C 3-31 As reaction proceeding, absorbance at 630 nm(derived from Cu(II)) of the reaction mixtures were decreasing. If, after the reaction, the reaction mixture is exposed to air, the absorbance of the solution will increase nearly to its initial value.this is evidence that Cu(I) is oxidized with oxygen to Cu(II). 11

13 2. olvent effect of tevens rearrangement(llis et al. J. Chem. oc., Perkin Trans 1, 1983, 1009.) 2 C 2 C * 2 C 2 C* base, solvent d 10 *=C 6 D :3-32-d 10 =1:1 intra- or intermolecular product 2 C 2 C* crossover(intermolecular) product 2 C* 2 C * * d d d C 2 C* 2 C* 2 C * * epi-3-33 epi-3-33-d 10 epi-3-33-d 5-1 epi-3-33-d 5-2 In more viscous solvent, the reaction exhibits lower intermolecularity and higher stereoselectivity. 12